Clinical scale production of an improved retroviral vector expressing the human multidrug resistance 1 gene (MDR1)
| Autor: | C. Lindemann, H G Eckert, A J Schilz, Klaus Kühlcke, A A Fauser, N Basara, Christopher Baum |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_treatment
Genetic Vectors CD34 Antineoplastic Agents Hematopoietic stem cell transplantation Mice SCID Transplantation Autologous Viral vector Cell Line Mice Mice Inbred NOD Cell Clone Neoplasms Autologous transplantation Medicine Animals Humans Transplantation business.industry Hematopoietic Stem Cell Transplantation Hematology Genetic Therapy Virology Retroviridae Cell culture Stem cell Genes MDR Safety business Biotechnology |
| Zdroj: | Bone marrow transplantation. 25 |
| ISSN: | 0268-3369 |
| Popis: | Retroviral vectors are currently the most important and best characterized tools for ex vivo genetic modification of hematopoietic progenitor/stem cells. As a prerequisite for clinical applications, large volumes of high-titer vector supernatants have to be generated in compliance with 'GMP' guidelines. This goal can be reached using a carefully selected producer cell clone and a conventional large-scale cell culture system. The retroviral vector SF1m provides efficient expression of the human multidrug resistance 1 (MDR1) gene in hematopoietic progenitor/stem cells in vitro and in NOD/SCID mouse repopulating human cells in vivo. Currently, a clinical phase I/II study is in preparation to test whether intensified consolidation chemotherapy is enabled by autologous transplantation of peripheral blood progenitor/stem cells that have been genetically modified with SF1m. Using multi-tray cell factories >19 l of serum-free vector containing supernatant were generated from cells of a previously established SF1m-producer clone, based on the PG13 packaging cell line. Testing of the final samples revealed sufficient quality (>1.5 x 10(6) infectious particles/ml) for clinical scale transduction of CD34+ cells. Results from the production runs and the applied biosafety concept are described. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|